Screening for Bowel Cancer

Transcription

1 Screening for Bowel Cancer Dr Bernard Ng, MBBS, FRANZCR

2 Learning objectives What are the Risk factors for bowel cancer? What are the evidence-based screening tools available for low and high risk patients? What are the deficiencies or controversies associated with each screening modality?

3 Epidemiology: Incidence 2010 MEN 1. Prostate 2. Bowel 3. Melanoma of the skin 4. Lung cancer 5. Lymphoid cancers WOMEN 1. Breast 2. Bowel 3. Melanoma of the skin 4. Lung cancer 5. Lymphoid cancers Excludes BCC and SCC of the skin AIHW Cancer Database and Cancer Australia

4 Epidemiology Colorectal cancer is common 2 nd or 3 rd most common cancer in most developed western countries 2 nd or 3 rd most common cancer related deaths Estimated Colorectal cancers diagnosed in 2012 (8760 males, 7080 females) Rectal cancer 1/ deaths from bowel cancer in 2012

5 Age-standardised incidence rate by year Age-standardised incidence rate MALES FEMALES Year of diagnosis Source: Australian Institute of Health and Welfare

6 Age-standardised mortality rate by year 40 Age-standardised mortality rate MALES FEMALES Year of death Source: Australian Institute of Health and Welfare

7 Epidemiology Risk increases after 40 yo Risk increases sharply after 50 yo (however increasingly affects all ages) In Risk of being diagnosed with bowel cancer by 85 years of age: 1 in 10 for males 1 in 15 for females

8 Age-specific incidence rates for 2011 Age-specific incidence rate MALES FEMALES Age group at diagnosis Source: Australian Institute of Health and Welfare

9 Risk factors

10 Types of CRC Mostly Sporadic ~ 80% Hereditary < 5% FAP ~ 1% Lynch Syndrome ~ 4% Others << 1% Peutz Jeghers Cowden s Bannayan Riley Ruvalcaba Family history 15-20% CRC being common = having a family member with CRC is common

11 What causes Sporadic CRC? Environmental Dietary low fibre, high animal fat Lifestyle smoking, +++ alcohol, physical inactivity Personal history / factors Increasing age Males > females Ethnicity Ashkenazi Jews Of cancer or polyps Metachronous cancer 0.3-1% per year Predisposing conditions IBD UC or Crohn s Esp if pancolitis, presence of primary sclerosing cholangitis Type 2 Diabetes emerging evidence, further research needed

12 Sporadic CRC at a Genetic level Sporadic CRC Adenomacarcinoma Sequence Epigenetic pathway via MLH1 MMR

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14 CRC Sporadic Hereditary Familial Adenoma Carcinoma Sequence* * Note differences in phenotype Epigenetics MLH1 Pathway* FAP HNPCC / Lynch Syndrome Hamartomatous syndromes Genetics not fully characterised but possibly related to an epigenetic event

15 Screening

16 Screening population Population screening to identify individuals at risk of colorectal carcinoma to warrant intervention NHMRC divides into 3 categories by family history and age Low risk Intermediate risk High risk Note these guidelines only apply to asymptomatic individuals. Once they develop symptoms, it is case finding, not screening

17 Screening tools Ideal screening tool: Simple Affordable acceptable FOBT Flexible sigmoidoscopy Colonoscopy (optical) CT colonography

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19 NHMRC 2005 Average to 2x increased risk (98%) Moderate (1-2%) 3-6 x increase High (~ 1%) Family History Recommend ations Strength of recommenda tion No personal history 1 FDR or SDR, > 55 yo 2 family members, opposite sides of family Standard person FOBT every 2 years from 50? Flex sig every 5 yrs FOBT strong Flex Sig - equivocal 1 FDR < 55 yo 2 FDR or 1 FDR + 1 SDR (same side) dx any age but w/o high risk features Colonoscopy every 5 years (or equivalent test) from 50 or 10 years younger than 1 st dx of CRC FOBT intervening yrs CT Colonography (non MBS ) CRC in 3 FDR/ FDR + SDR same side of family 2 FDR / SDR same side of family + multiple CRC in a family member, CRC < 50 yo, HNPCC related cancer Suspected FAP or known gene mutation Consider genetic counselling Colorectal surgeon / gastroenterologist for ongoing mx Depends on FAP or HNPCC

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25 National Bowel Cancer Screening Program - Govt (since 2006) Who is currently being invited to take part in the program 2015? Australians turning 50, 55, or 65, 70 and 74 years of age, who hold a Medicare card or DVA card Sent screening kit to be completed at home Budget: Between 2015 to 2020, planned to be increased to 2 yearly intervals from 50-74

26 (Non Govt) $39.95

27 The screening tools Benefits and Disadvantages

28 FOBT (Faecal Occult Blood Test) Systemic review of randomised controlled trials at population level Reduces mortality from colorectal cancer by 15-33%, and reduces incidence by 20% Cost effective: $24,660 cost per life year saved (Salkeld 1996) $25,000-$41, 667 per life year saved (Pignone 2011) < $50, 000 = cost effective intervention (PBS) Strongly recommended test for Low risk population

29 FOBT Guaiac test Immunochemical test Pseudoperoxidase activity of haem Antibodies against human haemoglobin Tradename: Hemoccult Tradename: HemSp (Bayer detect), OC Hemodia, Hemolex, Insure Reported Sensitivity 30-45% 60-90% Diet dependent (no red meat, specific fruit/ veg (eg: brocolli), vitamin C/ NSAID/aspirin for 3 days) Not influenced by diet

30 FOBT Positive FOBT: 30-45% chance of adenoma 13% Significant adenoma (>1cm or villous histopath) 1-5% chance of colorectal cancer 12-40x more likely to have colorectal cancer than a negative test Mandatory to investigate with colonoscopy

31 FOBT in Australia Population uptake: Australian Bowel Cancer Screening Participation 33.5% ( out of ) 7.5% (23 600) positive rate. 70% (16 500) went on to colonoscopy 52 confirmed cancer, 352 suspected cancer (3.2%) 728 advanced adenomas (5.7%) Polyps awaiting histopathology (41.2%) No abnormality (46%) Strongly recommended test for Low risk population

32 Flexible sigmoidoscopy Case-control studies. Appears to reduce mortality 31%. Sn: Can reach 50-60% of tumours. 60% of tumours are located on the left side Perforation risk 0.01%. Limited reach Alternative for low risk population 5 yearly

33 Colonoscopy Insufficient high level direct evidence of mortality reduction as primary screening tool Some case control studies Very accurate test Sensitivity:?100% Specificity: High. Allows biopsy May be incomplete 5% CT colonography (MBS indication) Suboptimal if poor prep Perforation risk %. 2.00% if therapeutic Limited resource, Cost

34 Colonoscopy Insufficient high level direct evidence of mortality reduction as primary screening tool Some case control studies Recommended for Screening for intermediate/high risk patients (not low risk patients) Investigation of positive FOBT Investigation of symptomatic patients

35 CT colonography Insufficient evidence for population screening, to reduce mortality Performance : ACRIN trials compared to colonoscopy Sensitivity 85-90%, Specificity 86%. Positive predictive value 23%, Negative predictive value 99% Recent biopsy or polypectomy generally wait 2-6 weeks to avoid exacerbating perforation Needs training and proper technique

36 Advantages of CTC Quick 5-7 min room time Sedation not required Little risk of perforation 0.009% - Not no risk NEJM 1999; 341:

37 Disadvantages of CTC Radiation. At age 50, CTC imparts 0.06% lifetime risk of radiation-related cancer; compared to 30% background chance of cancer Abdo discomfort, cramps. Buscopan visual blurring, glaucoma Flat polyps harder to see. Small polyps <5mm not as well seen Suboptimal if technical failure (prep, contrast, distension) Extracolonic findings incidentally found If lesion found Not therapeutic, not able to biopsy colonoscopy needed

38 CT colonography Recommended for Failed / incomplete conventional colonoscopy including obstruction (MBS date of colonoscopy stated <3/12) When colonoscopy relatively contraindicated because of significant medical conditions (non MBS) Not routinely recommended for Immediately after positive FOBT colonoscopy 1st choice (CT higher false positives and unable to biopsy) Preference (non MBS) Inflammatory bowel disease (pseudopolyps, need for biopsy) Genetic condition (high likelihood of abnormality needing biopsy)

39 CT Colonography: MBS rebate COMPUTED TOMOGRAPHY OF COLON for exclusion of colorectal neoplasia in symptomatic or high risk patients if: (a) the patient has had an incomplete colonoscopy in the 3 months before the scan; and (b) the date of incomplete colonoscopy is set out on the request for scan; and (c) the service is not a service to which items 56301, 56307, 56401, 56407, 56409, 56412, 56501, 56507, 56801, or applies (R) (K) COMPUTED TOMOGRAPHY OF COLON for exclusion of colorectal neoplasia in symptomatic or high risk patients if: (a) the request for scan states that one of the following contraindications to colonoscopy is present: (i) suspected perforation of the colon; (ii) complete or high-grade obstruction that will not allow passage of the scope; and (b) the service must not be a service to which item 56301, 56307, 56401, 56407, 56409, 56412, 56501, 56507, 56801, or applies (R) (K) NOT COVERED FOR MEDICALLY UNFIT FOR COLONOSCOPY

40 75% dose reduction with new low dose HD 750 CT scanner OLD SCANNER 8.5 msv NEW SCANNER 2.1 msv Background 3 msv a year

41 CT colonography: how is it done? Prep and oral contrast 2 days Insufflation (rectal tube) and scanning supine and prone Analysis and reporting

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43 Semiannular cancer

44 Small polyp 59mm

45 Double contrast barium enema Relatively cheap and available Much lower accuracy for polyps and cancer especially when small, compared to optical colonoscopy and CT colonography Replaced by CT colonography Not recommended first line in high or low risk populations

46 SUMMARY #1 What are the Risk factors for bowel cancer? Environmental Dietary low fibre, high animal fat Lifestyle smoking, +++ alcohol, physical inactivity Personal history / factors Increasing age Predisposing conditions IBD UC or Crohn s Family history Genetic conditions FAP, HNPCC

47 SUMMARY #2 What are the evidence-based screening tools available for low and high risk patients? Low risk FOBT (Flexi sig) Moderate and High risk Colonoscopy (CT colonography if not complete)

48 SUMMARY #3 What are the deficiencies or controversies associated with each screening modality?

49 FOBT (I) FLEXISIG COLONOSCOPY Evidence for primary screening role RCTs Mortality reduction Case control Mortality reduction Case control Insufficient good Insufficient good evidence evidence Sensitivity for polyp / cancer 60-90% ideal reported 60% (limited reach) About 100% 85-90% Sensitivity for advanced neoplasia? 32% 83% About 100% 96.7% Specificity About 50% High High 86% Advantages Cost effective Noninvasive High Sn and Sp Biopsy Therapeutic High Sn and Sp Fast No sedation Low complication Perforation risk % % % Disadvantages Patient uptake Variable Sn Limited reach Cost Cost Limited resource Radiation Cannot biopsy CT COLON

50 Questions